Risk Stratification and Treatment Selection in EGFR-Mutant NSCLC

This segment focuses on identifying clinical factors that influence the use of combination therapy for EGFR-mutant non-small cell lung cancer (NSCLC). Dr. Mark Socinski and Dr. Susan Scott discuss how treatment recommendations are tailored based on individual patient risk profiles. Dr. Scott highlights several features that may favor a more aggressive frontline approach, including brain metastases, liver metastases, high disease burden, persistent or detectable circulating tumor DNA (ctDNA), TP53 co-mutations, L858R mutations, younger age, and patient preference for maximizing long-term outcomes. At the same time, she emphasizes the importance of balancing efficacy with quality of life to avoid overtreatment in patients who may achieve durable benefit with osimertinib monotherapy. The discussion then transitions to disease progression after frontline osimertinib, introducing the evolving role of post-progression treatment strategies, including platinum-based chemotherapy, anti-angiogenic therapy, and emerging evidence from the COMPEL trial evaluating continuation of EGFR-targeted therapy beyond progression.